AMEBICA – PRODIGE 38

This open label, randomised (ratio 1:1), multicentre, phase II/III study assesses two chemotherapy regimens:

• Arm A: GEMCIS
• Arm B: Modified FOLFIRINOX (without 5FU bolus at D1)

Primary objective

• for phase II, to assess the percentage of patients alive without radiological
  progression at 6 months (assessed according to the RECIST 1.1 criteria)
• for phase III, to assess and to compare overall survival in the mFOLFIRINOX
  and GEMCIS arms

Secondary objectives

• The secondary objectives of the phase II study are:O
  • Overall survival
  • The best tumour response according to the RECIST 1.1 criteria
  • Toxicity (different types) (NCI-CTC version 4.0)
  • Biliary complications (angiocholitis, obstruction of the main bile ducts or biliary stent obstruction)
• The secondary objectives of the phase III study are:
  • Progression-free survival
  • The best tumour response according to the RECIST 1.1 criteria
  • Toxicity (different types) (NCI-CTC version 4.0)
  • Biliary complications (angiocholitis, obstruction of the main bile ducts or biliary stent obstruction)
  • Quality of life (EORTC QLQ-C30)

• WHO 0 or 1
• Age ≥ 18 years
• Tumour of the intrahepatic or extrahepatic (and/or hilar) bile ducts, or of the gallbladder
• Measurable abdominal metastases (at least a lesion >10 mm) and/or measurable, unresectable primary tumour
• Disease proven by histopathology or cytology (on metastasis or primary tumour)
• If there are no abdominal metastases, the unresectability must be confirmed by a hepatobiliary surgeon in a multidisciplinary team (MDT) meeting
• Bilirubin &lt;1.5 N (after endoscopic or trance hepatic optimum biliary drainage, if necessary), AST and ALT <10N
• Serum creatinine <130 µmol/L, creatinine clearance >60 mL/min
• Neutrophils ≥ 1500/mm3 and platelets ≥ 75,000/mm3
• Prothrombin index > 70%
• Serum albumin > 25 g/L
• Patient registered with a social security scheme (including CMU)
• Signed informed consent form

• Non-measurable metastases and primary tumour
• Ampullary carcinoma or cancer of the pancreas with infiltration of the bile ducts or mixed tumours (hepatocholangiocarcinoma)
• Chemotherapy and/or radiotherapy within the last 4 months
• Other malignant tumour except in situ basal cell carcinoma or curatively treated carcinoma of the uterine cervix or other malignant tumour that has been treated and has been considered cured for at least 5 years
• Major comorbidity factors (unstable angina, myocardial infarction that has occurred within the last 6 months, heart failure ≥2 according to the NYHA classification, uncontrolled high blood pressure)
• Woman who is pregnant or breastfeeding, or patient of either sex who is of childbearing age and not using an adequate contraceptive method - Not able to undergo the trial medical follow-up for geographical, social or psychological reasons.

Arm A: GEMCIS

At D1 and D8 of each cycle (every 21 days for 6 months)

• Cisplatin 25 mg/m² over 1 hour at D1 and D8 followed by gemcitabine 1000 mg/m² over 30 minutes at D1 and D8.

Arm B: Modified FOLFIRINOX = mFOLFIRINOX (without 5FU bolus at D1)

At D1 of each cycle (every 15 days for 6 months):

• Oxiplatin: 85 mg/m² (IP/120 minutes)
• Irinotecan 180 mg/m² (IV/90 minutes)
• Folinic acid: 400 mg/m² (or 200 mg/m² if Elvorine [calcium levofolinate]) (IV/2 hours), via a Y connector at the same time as irinotecan
• 5-FU: 2400 mg/m² (IV/46 hours)

Recruitment Start Date (FPI): 2018
Recruitment Finish Date (LPI): 2019
Follow-up Period End Date (LPO): 2025
End of trial is defined by the last patient last visit

Prof. Ivan Borbath, UCL Saint-Luc Bruxelles

FFCD

• ULB Erasme Bruxelles
• CHU-UCL Site Sainte Elisabeth Namur
• CHC Saint-Joseph Liège
• AZ Delta Roeselare